Retinoic Acid-PPARα Mediates ß-Carotene Resistance to Placental Dysfunction Induced by Deoxynivalenol.

Deoxynivalenol (DON), one of the most polluted mycotoxins in the environment and food, has been proven to have strong embryonic and reproductive toxicities. However, the effects of DON on placental impairment and effective interventions are still unclear. This study investigated the effect of ß-carotene on placental functional impairment and its underlying molecular mechanism under DON exposure. Adverse pregnancy outcomes were caused by intraperitoneal injection of DON from 13.5 to 15.5 days of gestation in mice, resulting in higher enrichment of DON in placenta than in other tissue samples. Interestingly, 0.1% ß-carotene dietary supplementation could significantly alleviate DON-induced pregnancy outcomes. Additionally, in vivo and in vitro placental barrier models demonstrated the association of DON-induced placental function impairment with placental permeability barrier disruption, angiogenesis impairment, and oxidative stress induction. Moreover, ß-carotene regulated DON-induced placental toxicity by activating the expressions of claudin 1, zonula occludens-1, and vascular endothelial growth factor-A through retinoic acid-peroxisome proliferator-activated receptor α signaling.

Dietary adenosine supplementation improves placental angiogenesis in IUGR piglets by up-regulating adenosine A2a receptor.

Abnormal placental angiogenesis is associated with the occurrence of intrauterine growth restriction (IUGR) in piglets, and effective treatment strategies against this occurrence remain to be explored. Adenosine has been reported to play an important role in angiogenesis, but its role in placental angiogenesis is still unknown. Here, we investigated the effect of dietary adenosine supplementation on IUGR occurrence in piglets by analyzing the role of adenosine in placental angiogenesis for Normal and IUGR piglets. Specifically, 88 sows were allotted to 2 treatments (n = 44) and fed a basal diet supplemented with 0% or 0.1% of adenosine from day 65 of gestation until farrowing, followed by collecting the placental samples of Normal and IUGR piglets, and recording their characteristics. The results showed that adenosine supplementation increased the mean birth weight of piglets (P < 0.05) and placental efficiency (P < 0.05), while decreasing the IUGR piglet rate (P < 0.05). Expectedly, the placenta for IUGR neonates showed a down-regulated vascular density (P < 0.05) and angiogenesis as evidenced by the expression level of vascular cell adhesion molecule-1 (VCAM1) (P < 0.05). Notably, dietary adenosine supplementation promoted angiogenesis (P < 0.05) both in the Normal and IUGR placenta. More importantly, the expression level of adenosine A2a receptor (ADORA2A) was lower (P < 0.05) in the IUGR placenta than in Normal placenta, whereas adenosine treatment could significantly increase ADORA2A expression, and also had an interaction effect between factors IUGR and Ado. Collectively, placentae for IUGR piglets showed impaired angiogenesis and down-regulated expression level of ADORA2A, while dietary adenosine supplementation could activate ADORA2A expression, improve the placental angiogenesis, and ultimately decrease the occurrence of IUGR in piglets.

Dietary fibers with low hydration properties exacerbate diarrhea and impair intestinal health and nutrient digestibility in weaned piglets.

BACKGROUND: This study aimed to investigate the hydration properties of different-source fibrous materials by comparing their water-binding capacity (WBC), water swelling capacity (WSC), viscosity, and in vivo effects of selected samples on growth performance, nutrient digestibility, diarrhea, and intestinal health in weaned piglets. METHODS: A total of 13 commercially available fibrous materials were first compared in chemical composition and in vitro hydration property. Subsequently, 40 weaned piglets were randomized to five experimental dietary groups (8 piglets per group): control diet (a basal diet without dietary fiber, CON), basal diet supplemented with 5% microcrystalline cellulose (MCC), 5% wheat bran (WB), 5% Moringa oleifera leaf powder (MOLP), or 5% sugar beet pulp (SBP), followed by analyzing their growth performance and diarrhea rate in a 28-d experiment. After the feeding experiment, anaesthetized piglets were killed, and their intestinal and colon content or plasma samples were analyzed in nutrient digestibility, intestinal morphology, intestinal barrier, short-chain fatty acids (SCFAs), and bacterial population. RESULTS: In vitro studies showed low hydration properties for WB and MCC, while medium hydration properties for MOLP and SBP. In vivo studies indicated that compared with medium hydration property groups, low hydration property groups showed (1) exacerbated diarrhea, impaired intestinal health, and reduced apparent fecal digestibility of dry matter, gross energy, acid detergent fiber, and neutral detergent fiber; (2) decreased SCFAs concentration and relative levels of Lactobacillus and Bifidobacterium, but increased levels of Escherichia coli and Brachyspira hyodysenteriae in colon contents. Additionally, SBP showed optimal performance in reducing diarrhea and increasing SCFAs production. Correlation analysis revealed a positive correlation of fiber hydration properties with in vitro SCFAs production, and diarrhea index and nutrient digestibility were negatively and positively correlated with SCFAs levels in the colon contents of weaned piglets, respectively. CONCLUSIONS: Different-source dietary fibers varied in their hydration properties and impacts on diarrhea, microbial composition and SCFAs production in weaned piglets. WB and MCC could exacerbate diarrhea and impair nutrient digestibility, probably because their low hydration properties were detrimental to gut microbial homeostasis and fermentation. Our findings provide new ideas for rational use of fiber resources in weaned piglets.

UPLC-Orbitrap-MS/MS Combined With Biochemical Analysis to Determine the Growth and Development of Mothers and Fetuses in Different Gestation Periods on Tibetan Sow Model.

Pregnancy is a complex and dynamic process, the physiological and metabolite changes of the mother are affected by different pregnancy stages, but little information is available about their changes and potential mechanisms during pregnancy, especially in blood and amniotic fluid. Here, the maternal metabolism rules at different pregnancy stages were investigated by using a Tibetan sow model to analyze the physiological hormones and nutrient metabolism characteristics of maternal serum and amniotic fluid as well as their correlations with each other. Our results showed that amniotic fluid had a decrease (P < 0.05) in the concentrations of glucose, insulin and hepatocyte growth factor as pregnancy progressed, while maternal serum exhibited the highest concentrations of glucose and insulin at 75 days of gestation (P < 0.05), and a significant positive correlation (P < 0.05) between insulin and citric acid. Additionally, T4 and cortisol had the highest levels during late gestation (P < 0.05). Furthermore, metabolomics analysis revealed significant enrichment in the citrate cycle pathway and the phenylalanine/tyrosine/tryptophan biosynthesis pathway (P < 0.05) with the progress of gestation. This study clarified the adaptive changes of glucose, insulin and citric acid in Tibetan sows during pregnancy as well as the influence of aromatic amino acids, hepatocyte growth factor, cortisol and other physiological indicators on fetal growth and development, providing new clues for the normal development of the mother and the fetus, which may become a promising target for improving the well-being of pregnancy.

Activation of PPARγ2 by PPARγ1 through a functional PPRE in transdifferentiation of myoblasts to adipocytes induced by EPA.

PPARγ and Wnt signaling are central positive and negative regulators of adipogenesis, respectively. Here we identified that, eicosapentaenoic acid (EPA) could effectively induce the transdifferentiation of myoblasts into adipocytes through modulation of both PPARγ expression and Wnt signaling. During the early stage of transdifferentiation, EPA activates PPARδ and PPARγ1, which in turn targets ß-catenin to degradation and down-regulates Wnt/ß-catenin signaling, such that the myogenic fate of myoblasts could be switched to adipogenesis. In addition, EPA up-regulates the expression of PPARγ1 by activating RXRα, then PPARγ1 binds to the functional peroxisome proliferator responsive element (PPRE) in the promoter of adipocyte-specific PPARγ2 to continuously activate the expression of PPARγ2 throughout the transdifferentiation process. Our data indicated that EPA acts as a dual-function stimulator of adipogenesis that both inhibits Wnt signaling and induces PPARγ2 expression to facilitate the transdifferentiation program, and the transcriptional activation of PPARγ2 by PPARγ1 is not only the key factor for the transdifferentiation of myoblasts to adipocytes, but also the crucial evidence for successful transdifferentiation. The present findings provided insight for the first time as to how EPA induces the transdifferentiation of myoblasts to adipocytes, but also provide new clues for strategies to prevent and treat some metabolic diseases.

EPA inhibits the inhibitor of κBα (IκBα)/NF-κB/muscle RING finger 1 pathway in C2C12 myotubes in a PPARγ-dependent manner.

The present study was conducted to evaluate the mechanism by which n-3 PUFA regulates the inhibitor of κBα (IκBα)/NF-κB/muscle RING finger 1 (MuRF1) pathway in C2C12 myotubes. After treatment with 150, 300 or 600 µm-α-linolenic acid (ALA) or -EPA for 24 h in C2C12 myotubes, the levels of phosphorylated IκBα (p-IκBα) and total IκBα were measured by Western blot. Compared with the bovine serum albumin (BSA) control, 150 and 300 µm-ALA and -EPA, respectively, did not affect the total IκBα protein level (P>0·05). However, 600 µm-EPA, but not 600 µm-ALA, prevented IκBα phosphorylation and increased the total IκBα levels (P < 0·01). Furthermore, total nuclear protein was isolated and analysed by the electrophoretic mobility shift assay for NF-κB DNA-binding activity after treatment with 600 µm-ALA or -EPA for 24 h. EPA (600 µm), but not ALA (600 µm), decreased the NF-κB DNA-binding activity when compared with BSA (P < 0·01). It was further observed that 600 µm-EPA caused a 3·38-fold reduction in the levels of MuRF1 mRNA expression compared with BSA (P < 0·01). Additionally, 600 µm-EPA resulted in a 2·3-fold induction of PPARγ mRNA expression (P < 0·01). In C2C12 myotubes, PPARγ knockdown by RNA interference significantly decreased PPARγ mRNA and protein expression to approximately 50 and 60% (P < 0·01), respectively. Interestingly, in C2C12 myotubes with PPARγ knockdown, 600 µm-ALA and -EPA did not affect the levels of p-IκBα and total IκBα, NF-κB DNA-binding activity or MuRF1 mRNA expression when compared with BSA (P>0·05). These results revealed that EPA, but not ALA, inhibited the IκBα/NF-κB/MuRF1 pathway in C2C12 myotubes in a PPARγ-dependent manner.

Methionine metabolism in piglets Fed DL-methionine or its hydroxy analogue was affected by distribution of enzymes oxidizing these sources to keto-methionine.

Previous evidence shows that the extensive catabolism of dietary essential amino acids (AA) by the intestine results in decreased availability of these AA for protein synthesis in extraintestinal tissues. This raises the possibility that extraintestinal availability of AA may be improved by supplying the animal with an AA source more of which can bypass the intestine. To test this hypothesis, six barrows (35-day-old, 8.6 +/- 1.4 kg), implanted with arterial, portal, and mesenteric catheters, were fed a DL-methionine (DL-MET) or DL-2-hydroxy-4-methylthiobutyrate (DL-HMTB) diet once hourly and infused intramesenterically with 1% p-amino hippurate. Although the directly available L-MET in DL-MET diet was about 1.2-fold that in DL-HMTB diet, the net portal appearance of L-MET was not different between the two diets. Compared with the low mRNA abundance and low activity of D-2-hydroxy acid dehydrogenase (D-HADH) and l-2-hydroxy acid oxidase (L-HAOX) in the intestine, the high mRNA abundance and high activity of D-AA oxidase (D-AAOX) indicated that the intestine had a relatively higher capacity of D-MET utilization than of dl-HMTB utilization to L-MET synthesis and its subsequent metabolism. However, in contrast to the much lower D-AAOX activity (nmol/g tissue) in the stomach than in the liver and kidney, both d-HADH and L-HAOX activity in the stomach was comparable with those in the liver and/or kidney, indicating the substantial capacity of the stomach to convert DL-HMTB to L-MET. Collectively, the difference in distribution of activity and mRNA abundance of D-AAOX, D-HADH, and L-HAOX in the piglets may offer a biological basis for the similar portal appearance of L-MET between DL-MET and DL-HMTB diets, and thus may provide new important insights into nutritional efficiency of different L-MET sources.

The effect of linseed on intramuscular fat content and adipogenesis related genes in skeletal muscle of pigs.

The aim of the study was to investigate the effect of n-3 PUFA enrichment in longissimus muscle on intramuscular fat (IMF) content and expression of related genes in growing-finishing barrows. Two isoenergetic, isonitrogenous and isolipidic diets were formulated: one was basal diet and the other contained 10% linseed. Twenty-four Landrace x NewDamLine barrows weighing 35 +/- 3.7 kg were randomly assigned to four treatment groups with six pigs per group. During the whole experimental period of 90 days, all groups were first fed the basal diet and then the linseed diet for 0, 30, 60, and 90 days before slaughter, respectively. Meat quality, fatty acid composition, and expression of genes involved in adipogenesis in longissimus muscle were measured and analyzed. The IMF content increased linearly (P < 0.05) as the linseed diet feeding time prolonged. Meanwhile, n-3 PUFA content and expression of peroxisome proliferator-activated receptor delta (PPARdelta), PPARgamma, adipocyte fatty acid-binding protein (aP2) and lipoprotein lipase (LPL) increased linearly (P < 0.01) as well, while the expression of wingless related MMTV integration site 10b (Wnt10b) linearly decreased (P < 0.01). Furthermore, significant (P < 0.01) quadratic or linear relation was observed between n-3 PUFA enrichment and expression of these genes, while significant (P < 0.01) quadratic or linear relation was observed between the expression of PPARgamma, aP2 or Wnt10b and IMF content. These data show that enhancing n-3 PUFA enrichment in muscle leads to significant increase in IMF content. A possible explanation is due to alterations in the expression of genes involved in adipogenesis, however this will need to be confirmed by protein and enzyme activity studies.